Transcutaneous auricular Vagal Nerve Stimulation (taVNS) is a non-invasive brain stimulation technique associated with possible modulation of norepinephrinergic (NE) activity. NE is suspected to contribute to generation of the P3 event-related potential. Recent evidence has produced equivocal evidence whether taVNS influences the P3 in healthy individuals during oddball tasks. We examined the effect of taVNS on P3 amplitudes using a novel visual Bayesian oddball task, which presented 200 sequences of three stimuli. The three consecutive stimuli in each sequence are labelled Draw 1, Draw 2 and Draw 3. In total, 47 Subjects completed this visual Bayesian oddball task under randomised sham and active taVNS stimulation in parallel with an electroencephalographic (EEG) recording. We conducted exploratory analyses of the effect of taVNS on P3 amplitudes separately for Draws. We found typical oddball effects on P3 amplitudes at Draws 1 and 2, but not Draw 3. At Draw 2, the oddball effect was enhanced during active compared to sham taVNS stimulation. These data provide evidence that taVNS influences parietal P3 amplitudes under specific circumstances. Only P3 amplitudes at Draw 2 were affected, which may relate to closure of Bayesian inference after Draw 2. Our findings seemingly support previously reported links between taVNS and the NE system.

Objectives: Gilles de la Tourette syndrome (GTS) is a neuropsychiatric condition characterized by motor and vocal tics. There is undoubtedly basal ganglia involvement, which are also important for cognitive processes including performance monitoring and interference resolution. We investigated these functions in adult patients with GTS compared to healthy controls (HCs). Methods: We compared a group of N = 23 adult patients with GTS to N = 27 HC on a flanker task during an EEG recording. Reaction times and error rates were recorded, as well as N2 and Ne/ERN amplitudes. The N2 is an index of interference resolution. The Ne/ERN is a negative fronto-central component, occurring when participants make mistakes. Results: Patients' reaction times were enhanced on incongruent trials compared to HC. Electrophysiological data revealed more frontal components, as well as significantly increased Ne/ERN amplitudes in patients with GTS compared to HC (p = .026).

Objective: Parkinson's Disease (PD) is a neurodegenerative disease caused by the loss of dopaminergic neurons. Cognitive impairments have been reported using the event-related potential (ERP) technique. Patients show reduced novelty P3 (nP3) amplitudes in oddball experiments, a response to infrequent, surprising stimuli, linked to the orienting response of the brain. The nP3 is thought to depend on dopaminergic neuronal pathways though the effect of dopaminergic medication in PD has not yet been investigated.Methods: Twenty-two patients with PD were examined "on" and "off" their regular dopaminergic medication in a novelty 3-stimulus-oddball task. Thirty-four healthy controls were also examined over two sessions, but received no medication. P3 amplitudes were compared throughout experimental conditions.Results: All participants showed sizeable novelty difference ERP effects, i.e. ndP3 amplitudes, during both testing sessions. An interaction of diagnosis, medication and testing order was also found, indicating that dopaminergic medication modulated ndP3 in patients with PD across the two testing sessions: We observed enhanced ndP3 amplitudes from PD patients who were off medication on the second testing session. Conclusion:Patients with PD 'off' medication showed ERP evidence for repetition-related enhancement of novelty responses. Dopamine depletion in neuronal pathways that are affected by mid-stage PD possibly accounts for this modulation of novelty processing.Significance: The data in this study potentially suggest that repetition effects on novelty processing in patients with PD are enhanced by dopaminergic depletion. Highlights:(1)All participants showed robust novelty P3 waveforms during both testing sessions.(2) Patients who were tested on medication during a first session, showed enhanced novelty P3 amplitudes during a second session (off medication).(3) Our results demonstrate the necessity for properly controlled repeated-measures designs to isolate diagnosis or medication effects and novelty or repetition effects.

Background Antidepressants are established as an evidence-based, guideline-recommended treatment for Major Depressive Disorder. Prescriptions have markedly increased in past decades, with a specific surge in maintenance prescribing. Patients often remain on antidepressants longer than clinically necessary. When attempting to stop, many patients experience adverse discontinuation symptoms. Discontinuation symptoms can be debilitating and hinder successful discontinuation. While discontinuation symptoms can result from pharmacological effects, evidence on nocebo-induced side effects of antidepressant use suggests that patients' expectations may also influence occurrence. Methods To disentangle pharmacological and expectation effects in antidepressant discontinuation, patients with fully remitted Major Depressive Disorder who fulfill German guideline recommendations to discontinue will either remain on or discontinue their antidepressant. Participants' expectations will be manipulated by varying verbal instructions using an open-hidden paradigm. Within the open trial arms, participants will receive full information about treatment, i.e., high expectation. Within the hidden trial arms, participants will be informed about a 50% chance of discontinuing versus remaining on their antidepressant, i.e., moderate expectation. A total of N = 196 participants will be randomly assigned to either of the four experimental groups: open discontinuation (OD; n = 49), hidden discontinuation (HD; n = 49), open continuation (OC; n = 49), or hidden continuation (HC; n = 49). Discontinuation symptom load during the 13-week experimental phase will be our primary outcome measure. Secondary outcome measures include discontinuation symptom load during the subsequent 39-week clinical observation phase, recurrence during the 13-week experimental period, recurrence over the course of the complete 52-week trial evaluated in a time-to-event analysis, and stress, anxiety, and participants’ attentional and emotional processing at 13 weeks post-baseline. Blood and saliva samples will be taken as objective markers of antidepressant blood serum level and stress. Optional rsfMRI measurements will be scheduled. Discussion Until today, no study has explored the interplay of pharmacological effects and patients’ expectations during antidepressant discontinuation. Disentangling their effects has important implications for understanding mechanisms underlying adverse discontinuation symptoms. Results can inform strategies to manage discontinuation symptoms and optimize expectations in order to help patients and physicians discontinue antidepressants more safely and effectively. Trial registration ClinicalTrials.gov (NCT05191277), January 13, 2022.

ImportanceUptake of vaccination against COVID-19 is strongly affected by concerns about adverse effects. Research on nocebo effects suggests that these concerns can amplify symptom burden.ObjectiveTo investigate whether positive and negative expectations prior to COVID-19 vaccination are associated with systemic adverse effects.Design, Setting, and ParticipantsThis prospective cohort study analyzed the association of expected benefits and risks of vaccination, adverse effects at first vaccination, and observed adverse effects in close contacts with severity of systemic adverse effects among adults receiving a second dose of messenger RNA (mRNA)–based vaccines between August 16 and 28, 2021. A total of 7771 individuals receiving the second dose at a state vaccination center in Hamburg, Germany, were invited to participate; of these, 5370 did not respond, 535 provided incomplete information, and 188 were excluded retrospectively. The mobile application m-Path was used for data collection.Main Outcomes and MeasuresPrimary outcome was a composite severity index of systemic adverse effects in 12 symptom areas measured once daily with an electronic symptom diary over 7 consecutive days. Data were analyzed by mixed-effects multivariable ordered logistic regression adjusted for prevaccine symptom levels and observation times.ResultsA total of 10 447 observations from 1678 individuals receiving vaccinations (BNT162b2 [Pfizer BioNTech] in 1297 [77.3%] and mRNA-1273 [Moderna] in 381 [22.7%]) were collected. The participants’ median age was 34 (IQR, 27-44) years, and 862 (51.4%) were women. The risk for more severe adverse effects was higher for persons expecting a lower benefit of vaccination (odds ratio [OR] for higher expectations, 0.72 [95% CI, 0.63-0.83]; P < .001), expecting higher adverse effects of vaccination (OR, 1.39 [95% CI, 1.23-1.58]; P < .001), having experienced higher symptom burden at the first vaccination (OR, 1.60 [95% CI, 1.42-1.82]; P < .001), scoring higher on the Somatosensory Amplification Scale (OR, 1.21 [95% CI, 1.06-1.38]; P = .004), and if the vaccine mRNA-1273 was given rather than BNT162b2 (OR, 2.45 [95% CI, 2.01-2.99]; P < .001). No associations were seen for observed experiences.Conclusions and RelevanceIn this cohort study, several nocebo effects occurred in the first week after COVID-19 vaccination. The severity of systemic adverse effects was associated not only with vaccine-specific reactogenicity but also more negative prior experiences with adverse effects from the first COVID-19 vaccination, more negative expectations regarding vaccination, and tendency to catastrophize instead of normalize benign bodily sensations. Clinician-patient interactions and public vaccine campaigns may both benefit from these insights by optimizing and contextualizing information provided about COVID-19 vaccines.